Sterilization method for hollow fiber membrane filters

Abstract

The present invention relates to a method for sterilizing a hollow fiber membrane filter with a sterilizing fluid such as water or steam, the method comprising a rinsing step, a sterilization step, and a leak test to ensure better sterilization reliability of the hollow fiber membrane filter.

Description

Technical Field

[0001]

[0001] The subject matter of the present application is a method for sterilizing a hollow fiber membrane filter used for extracorporeal blood treatment of patients with kidney diseases.

Background Art

[0002]

[0002] Hollow fiber membranes used in blood purification are often made from polysulfone (PSU) and polyvinylpyrrolidone (PVP) because these materials have been found to have particularly good blood compatibility and are thus preferred from a medical perspective for blood treatment, especially hemodialysis.

[0003]

[0003] In the production of such hollow fiber membranes, the spinning material is extruded through a nozzle to form hollow spun yarns, which are then introduced into a precipitation bath, usually consisting of water. To form the pore structure, an aqueous precipitant containing an aprotic solvent, such as dimethylacetamide, N-methylpyrrolidone, dimethylformamide, or dimethylsulfoxide, is used. The resulting hollow fiber membrane is then passed through a rinsing bath, dried, and wound onto a reel. The hollow fiber membrane can be removed from the reel in the form of a hollow fiber membrane bundle. For the construction of a hollow fiber membrane filter, such a hollow fiber membrane bundle is then placed into a housing, preferably a cylindrical housing. Both ends of the hollow fiber membrane bundle are embedded in a potting material, and the open ends of the hollow fibers are exposed. The potting material forms a sealing region between the interior of the hollow fiber membrane, the housing, and the space surrounding the hollow fiber membrane. Thereby, a first compartment is formed within the hollow fiber membrane filter, which includes the inlet and outlet regions at both ends of the hollow fiber membrane bundle and also the interior of the hollow fiber membrane. Correspondingly, a second compartment is formed in the space between the hollow fibers and between the housing wall and the hollow fiber membrane. The fluid inlet of the housing of the hollow fiber membrane filter enables liquids and fluids to be supplied to and discharged from the first and / or second compartments of the hollow fiber membrane filter.

[0004]

[0004] Hollow fiber membrane filters provided for extracorporeal blood treatment typically include first and second fluid inlets in a first compartment of the filter module and first and second fluid inlet ports in a second compartment of the filter module. Thus, fluids, particularly liquids or gases, can be supplied or discharged through the first inlet of the compartment of the hollow fiber membrane filter depending on the direction of flow, or through the second inlet of the compartment of the hollow fiber membrane filter corresponding to the direction of flow.

[0005]

[0005] In the case of hollow fiber membrane filters intended for medical use, particularly for blood treatment in patients with kidney disease, the hollow fiber membrane manufacturing process and filter construction are usually followed by one or more rinsing and sterilization steps to wash and sterilize the hollow fiber membrane for medical use.

[0006]

[0006] According to the prior art, processes are known in which hollow fiber membranes in hollow fiber membrane filters are subjected to rinsing and sterilization steps. In particular, heat sterilization with water or steam is a well-known sterilization process for hollow fiber membranes and hollow fiber membrane filters. Heat sterilization is understood to mean sterilization with a fluid (e.g., water or steam or a mixture thereof) at a temperature above 100°C. Heat sterilization with remarkably pure steam is also called steam sterilization.

[0007]

[0007] A corresponding process for sterilizing a dialyzer is described in DE3936785C1. According to this procedure, the dialyzer is first subjected to a rinsing process and then to a sterilization process. During the sterilization process, the dialyzer is rinsed with water or steam heated to over 121°C. Heat sterilization carried out according to DE3936785C1 has proven to be superior to other sterilization methods in terms of technical equipment and process technology.

[0008]

[0008] WO2018 / 204498A9 describes a sterilization process for hollow fiber membrane filters containing polysulfone and polyvinylpyrrolidone hollow fiber membranes. The described sterilization process uses a process step in which water vapor passes through the membrane wall by adjusting the pressure ratio in first and second compartments of the hollow fiber membrane filter.

[0009]

[0009] Processes known in the prior art are designed so that further process steps follow the actual sterilization step. In particular, in these procedures, leak testing of the hollow fiber membrane filter was performed downstream of the sterilization step. Leak testing performed during steam sterilization of the hollow fiber membrane filter is usually performed as a so-called "bubble point test." In this test, sterile compressed air is filled into the second compartment of the hollow fiber membrane filter as defined above, or alternatively, sterile compressed air flows through it. Highly purified water is filled into or flows through the second compartment of the hollow fiber membrane filter. The upstream step fills the pores of the hollow fiber membrane with water. The pressure of the sterile compressed air in the "bubble point test" is selected so that it does not exceed the surface tension of the water in the pores and that the water remains in the pores. However, if a leak exists between the first and second compartments of the hollow fiber membrane filter, at the set pressure, sterile compressed air will leak into the first compartment and be discharged from the first compartment along with the highly purified water flowing through it. A bubble detector connected to the outlet of the first compartment of the hollow fiber membrane filter can detect leaked sterile compressed air, and accordingly, the hollow fiber membrane filter can be sorted in the process.

[0010]

[0010] A drawback described in the prior art is that the leak test is performed after the actual sterilization step. Therefore, the quality of the sterilization of the filter needs to be further improved. However, in addition to that, hollow fiber membrane filters that exhibit leaks due to production are not permitted for use in medical applications, so the integrity of the hollow fiber membrane filter, and therefore the performance of the leak test, is of paramount importance. Object of the Invention

[0011]

[0011] In relation to the problems common in the prior art, the objective is to provide a process for sterilizing hollow fiber membrane filters that is based on the principles of steam and heat sterilization, has high sterilization quality, and also guarantees the integrity of the hollow fiber membrane filters. [Overview of the Initiative]

[0012]

[0012] The object of the present invention is solved by the method described in claim 1. Claims 2 to 14 represent preferred embodiments of the method. Description of the Invention

[0013]

[0013] The present invention will be described below with reference to individual embodiments, and will be illustrated with reference to Figures 1 to 4.

[0014]

[0014] The present invention relates to a method for sterilizing a hollow fiber membrane filter having a plurality of hollow fiber membranes, wherein the plurality of hollow fiber membranes are sealed at both ends within a housing of a hollow fiber membrane filter such that a first compartment including the interior of the hollow fiber membranes and a second compartment including the space between the hollow fiber membranes are formed, and the hollow fiber membrane filter has at least two fluid inlets connected to the first compartment and at least two fluid inlets connected to the second compartment, the fluid inlets are configured to be connected to a sterilization device. The method is The method comprises at least the steps of: rinsing a hollow fiber membrane filter with a fluid, particularly water, wherein the rinsing fluid passes through a first compartment and a second compartment of the hollow fiber membrane filter via a fluid inlet selection; and performing a leak test; and sterilizing the hollow fiber membrane filter with a sterilizing fluid, particularly heated water or steam, wherein the sterilizing fluid passes through a first compartment and a second compartment of the hollow fiber membrane filter via a fluid inlet selection, wherein the leak test is performed before the sterilization step.

[0015]

[0015] In a further embodiment, the method according to the present invention is characterized in that, in a leak test, sterile compressed air is introduced into a second compartment of the hollow fiber membrane filter, particularly through, and highly purified water is introduced into a first compartment of the hollow fiber membrane filter, particularly through, and the pressure in the second compartment is higher than the pressure in the first compartment.

[0016]

[0016] According to the method of the present invention, the sterilization step is performed after the leak test. This ensures that there is no further rinsing step after the sterilization step that could potentially re-contaminate the hollow fiber membrane filter with bacteria, for example, during the leak test process. [Brief explanation of the drawing]

[0017] [Figure 1] A schematic diagram of the rinsing step of the method according to the present invention is shown. [Figure 2] A schematic diagram of the leak test step of the method according to the present invention is shown. [Figure 3] A schematic diagram of the sterilization step of the method according to the present invention is shown. [Figure 4] A schematic diagram of the blowout step is shown. [Modes for carrying out the invention]

[0018]

[0017] Figure 1 shows a schematic diagram of the rinsing step of the method according to the present invention. A hollow fiber membrane filter 101 having two fluid inlets 102a, 102b is shown, these fluid inlets provide access to a second compartment 120 of the hollow fiber membrane filter 101. Only one of a number of hollow fiber membranes is schematicly shown in Figure 1. Fluid inlets 103a, 103b are shown, forming access to a first compartment 110 of the hollow fiber membrane filter. The fluid inlets 102a, 102b, 103a, 103b are connected to a sterilization device (not shown in Figure 1) via connecting devices 150A, 150B, 150C, 150D. A flow of highly purified water is provided through the sterilization device and introduced into the second and first compartments 120, 110 of the hollow fiber membrane filter 101 via connecting devices 150A, 150B and fluid inlets 102b, 103b. Highly purified water flows through the first and second compartments 110 and 120, according to the embodiment of Figure 1. Therefore, the hollow fiber membrane filter is pre-prepared for the subsequent sterilization step. Within the scope of this application, highly purified water such as that described in the European Pharmacopoeia PH.EUR.04 / 2017:0169 is used.

[0019]

[0018] The temperature of the inflowing highly purified water is 85°C according to the illustrated embodiment. However, generally, depending on the design of the hollow fiber membrane filter, highly purified water at other temperatures such as 50-120°C, 50-95°C, 60-90°C, 65-90°C, or 70-90°C can be set in the rinsing step. The highly purified water exits the first and second compartments 110, 120 via fluid inlets 103a, 102a and connecting devices 150C, 150D and is discharged as wastewater.

[0020]

[0019] The duration of the rinsing step is preferably 40 seconds (s). Depending on the design of the hollow fiber membrane filter, alternative durations for the rinsing step, such as 20-60 s, 30-60 s, 35-50 s, or 35-45 s, may be used.

[0021]

[0020] During the rinsing step, all air is expelled from the hollow fiber membrane filter, which means that air in the first and second compartments 110, 120 of the hollow fiber membrane filter, in particular air from the pores of the membrane wall of the hollow fiber membrane, is also expelled.

[0022]

[0021] Figure 2 shows a schematic diagram of the leak test step of the method according to the present invention. In the illustrated embodiment, the leak test is performed as a so-called "bubble point test". The arrangement of the connecting devices 150A, 150B, 150C, 150D connected to the sterilization device (not shown in Figure 2) and the hollow fiber membrane filter is the same as in Figure 1. In the schematically illustrated process step of the leak test, highly purified water is supplied via the sterilization device and introduced into the first compartment 110 of the hollow fiber membrane filter via the connecting device 150B and the fluid inlet 103b. In this embodiment, the highly purified water has a temperature of 50°C and a pressure of 1 bar. The temperature can be varied depending on the design of the hollow fiber membrane filter and may be in the range of 30-70°C, 40-60°C, or 45-55°C. The pressure may be correspondingly 0.5-1.5 bar or 0.9-1.1 bar. Sterile compressed air flows into the second compartment of the hollow fiber membrane filter via the connecting device 150D and the fluid inlet 102a. In the illustrated embodiment, the pressure of the sterile compressed air is 2 bar, which can be varied between 1.5 and 3.5 bar depending on the design of the hollow fiber membrane filter and the pore size of the hollow fiber membrane. Highly purified water passes through the first compartment 110 and is discharged via the fluid inlet 103a and the connecting device 150C. Sterile compressed air passes through the second compartment 120 of the hollow fiber membrane filter 101 and is discharged via the fluid inlet 102b and the connecting device 150A. In the illustrated embodiment, sterile compressed air and highly purified water pass through the second and first compartments 120 and 110 of the hollow fiber membrane filter, respectively, using the principle of counterflow. If there is a leak between the first and second compartments, the sterile compressed air will leak from the second compartment 120 to the first compartment 110 and can be detected. Therefore, an optical detector is attached to the wastewater conduit 104, which is attached to the connecting device 150C and is in fluid communication with the first compartment 110 of the hollow fiber membrane filter 101. If there is a leak, compressed air entering the first compartment is discharged from the first compartment of the hollow fiber membrane filter as bubbles along with highly purified water, and can be optically detected by a suitable detector in the wastewater line.

[0023]

[0022] When it is determined that there is no leakage in the hollow fiber membrane filter, the second compartment 120 of the hollow fiber membrane filter 101 is filled with air after the leakage test, and the first compartment is filled with highly purified water. Further, the pores of the membrane wall of the hollow fiber are also filled with highly purified water.

[0024]

[0023] FIG. 3 shows a schematic view of the sterilization step of the method according to the present invention. The connection devices 150A, 150B, 150C, 150D connected to a sterilization device (not shown in FIG. 3), and the arrangement of the hollow fiber membrane filter are the same as those in FIGS. 1 and 2. In the sterilization step, highly purified water vapor is introduced into the first compartment 110 and the second compartment 120 of the hollow fiber membrane filter 101 through the connection devices 150C and 150D and the fluid inlets 103a and 102a. The highly purified water vapor is provided through a sterilization device and has a temperature of 123° C. and a pressure of 1.3 bar according to the illustrated embodiment. However, depending on the design of the hollow fiber membrane filter, other pressures and temperatures may be used to ensure optimal sterilization results. In particular, pressures of 1.1 to 3 bar, or 1.1 to 2.5 bar, or 1.1 to 2 bar, or 1.1 to 1.8 bar, or 1.2 to 1.6 bar may also be used in the sterilization step. Alternative temperatures of the highly purified water vapor range from 105 to 150° C., or 110 to 140° C., or 115 to 130° C. The highly purified water vapor passes through the first compartment 110 and the second compartment 120 of the hollow fiber membrane filter, whereby the first compartment and the second compartment are sterilized. When the highly purified water vapor passes through the first and second compartments, the highly purified water vapor cools and condenses a part of the highly purified water vapor. In the technical process, the mixture of the highly purified water vapor and the condensed water is called condensate and is discharged from the second compartment and the first compartment through the fluid inlets 102b, 103b and the connection devices 150A and 150B. In one embodiment, the duration of the sterilization step is 900 s. Depending on the design of the hollow fiber membrane filter, different durations of the sterilization step, for example, 200 to 1400 s, or 400 to 1100 s, or 400 to 800 s may be provided.

[0025]

[0024] In a further embodiment, the method according to the invention is characterized in that the introduction, in particular the passage, of sterile compressed air into / through the second compartment of the hollow fiber membrane filter and the introduction, in particular the passage, of highly purified water into / through the first compartment are carried out in countercurrent during the leak test.

[0026]

[0025] In a further embodiment, the process according to the invention is characterized in that the temperature of the water passing through the first and second compartments of the hollow fiber membrane filter is between 50 and 120 °C, or between 50 and 95 °C, or between 60 and 90 °C, or between 65 and 90 °C, or between 70 and 90 °C.

[0027]

[0026] In a further embodiment, the process according to the invention is characterized in that the sterilizing fluid is steam, in particular highly purified steam having a temperature of 105 to 150 °C, and the steam is introduced into the first and second compartments of the hollow fiber membrane filter at a pressure of 1.1 to 3 bar. In particular, pressures of 1.1 to 2.5 bar, or 1.1 to 2 bar, or 1.1 to 1.8 bar, or 1.2 to 1.6 bar can also be used in the sterilization step. Alternative temperatures for the highly purified steam can be in the range of 110 to 140 °C or 115 to 130 °C.

[0028]

[0027] In a further embodiment, the method according to the invention is characterized in that a blow - out step with sterile compressed air is carried out between the leak test and the sterilization step, and the first and second compartments of the hollow fiber membrane filter are blown out with sterile compressed air.

[0029]

[0028] Figure 4 shows a schematic diagram of this blowout step. The arrangement of the connecting devices 150A, 150B, 150C, 150D connected to the sterilization device (not shown in Figure 4) and the hollow fiber membrane filter is the same as in Figures 1 to 3. Figure 4 schematicly shows that the sterilized compressed air is introduced and passes through the first and second compartments 110, 120 of the hollow fiber membrane filter via the connecting devices 150C and 150D and the fluid inlets 103a, 102a. The sterilized compressed air is discharged as exhaust from the first and second compartments 110, 120 of the hollow fiber membrane filter via ports 103b and 102b and the respective connecting devices 150B and 150A. The pressure of the sterilized compressed air flowing into the first and second compartments 110, 120 is substantially the same, for example, 1 to 2 bar. The blowout step discharges any residual water remaining from the leak test from the first compartment 110 of the hollow fiber membrane filter. However, the pores in the membrane wall of the hollow fiber membrane preferably remain filled with water. Thus, the filter is advantageously prepared for the subsequent steam sterilization step. Depending on the design of the hollow fiber membrane filter, the blowout step may be performed for a duration of 30–90 s, 40–80 s, or 50–70 s.

[0030]

[0029] In further embodiments, the method according to the present invention is characterized in that, prior to the leak test, a steam extrusion step is performed in which steam enters, in particular through, the first and second compartments of the hollow fiber membrane filter. The steam extrusion step is performed according to the schematic diagram shown in Figure 3. In the steam extrusion step, highly purified steam is introduced into the first compartment 110 and the second compartment 120 of the hollow fiber membrane filter, respectively, via connecting devices 150C and 150D and fluid inlets 103a and 102a. The highly purified steam is supplied via a sterilization device and, according to the illustrated embodiment, has a temperature of 123°C and a pressure of 1.3 bar. However, other pressures and temperatures may be provided depending on the design of the hollow fiber membrane filter. In particular, pressures of 1.1 to 3 bar, or 1.1 to 2.5 bar, or 1.1 to 2 bar, or 1.1 to 1.8 bar, or 1.2 to 1.6 bar may also be used in the steam extrusion step. Preferably, the pressure of the highly purified steam in the first and second compartments of the hollow fiber membrane filter during the steam extrusion step is substantially the same. The alternative temperature of the highly purified steam may be in the range of 50–150°C, or 105–150°C, or 110–140°C, or 115–130°C. The highly purified steam passes through the first compartment 110 and the second compartment 120 of the hollow fiber membrane filter, thereby regulating the first and second compartments. As the highly purified steam passes through the first and second compartments, it cools and condenses a portion of it. In the technical process, the mixture of highly purified steam and condensed water is called condensate and is discharged from the second and first compartments via fluid inlets 102b, 103b and connecting devices 150A and 150B. Depending on the design of the hollow fiber membrane filter, different durations of the steam extrusion step may be provided, for example, 40–140 s, 50–110 s, or 60–100 s. The steam extrusion step pre-conditions the hollow fiber membrane filter with respect to temperature and pressure for the subsequent sterilization step. This makes it easier to identify potential leaks in subsequent leak tests before the sterilization step.

[0031]

[0030] In the above-described embodiment, the method according to the present invention is further characterized in that the introduction, in particular the passage, of water vapor into the first and second compartments of the hollow fiber membrane filter in the water vapor extrusion step is carried out according to the equal flow principle.

[0032]

[0031] In further embodiments, the method according to the present invention is characterized in that the water vapor in the first and second compartments of the hollow fiber membrane filter has substantially the same pressure, or the water vapor in the first compartment has a higher pressure than the water vapor in the second compartment. The pressures in the first and second compartments can be varied during the water vapor extrusion step. In particular, a higher pressure in the first compartment may cause transmembrane movement of highly purified water vapor from the first compartment to the second compartment. For example, clogging in the pores of the membrane can be removed, the hollow fiber membrane in the hollow fiber membrane filter can be loosened, thereby increasing the separation performance of the hollow fiber membrane filter in filtration applications and consequently increasing the clearance. Therefore, the pressure in the first compartment may be provided to be 1.5 bar, 1.3 bar, or 0.8 bar higher than the pressure in the second compartment, in which case the pressure in the second compartment may be 0.3 bar, 1.3 bar, or 1.5 bar.

[0033]

[0032] In a further embodiment of the method according to the present invention, a purging step is provided between the steam extrusion step and the leak test. This is advantageous as it allows the deposits and particles loosened by the steam extrusion step to be discharged from the hollow fiber membrane filter before the leak test and sterilization steps.

[0034]

[0033] In a further embodiment of the method according to the present invention, a first blowout step is provided in which the first and second sections of the hollow fiber membrane filter are blown out with sterile compressed air, which is performed before the steam extrusion step.

[0035]

[0034] The first blowout step is carried out in the same manner as schematically illustrated in Figure 4. The arrangement of the connecting devices 150A, 150B, 150C, 150D connected to the sterilization device (not shown in Figure 4) and the hollow fiber membrane filter is the same as in Figures 1 to 3. Figure 4 schematically shows that sterile compressed air is introduced and passes through the second and first compartments 120, 110 of the hollow fiber membrane filter via the connecting devices 150D and 150C and the fluid inlets 102a, 103a. The sterile compressed air is discharged as exhaust from the first and second compartments 110, 120 of the hollow fiber membrane filter via ports 103b and 102b and the respective connecting devices 150B and 150A. The pressure of the sterile compressed air flowing into the first and second compartments 110, 120 is substantially equal, for example, 1 to 2 bar. The first blowout step pre-dries the hollow fiber membrane filter for the subsequent steam extrusion step. Depending on the design of the hollow fiber membrane filter, the first blowout step may be performed over a duration of 30–90 s, 40–80 s, or 50–70 s.

[0036]

[0035] In further embodiments, the method according to the present invention is characterized in that, following the sterilization step, a drying step is performed in which sterile compressed air passes through the first and second compartments of the hollow fiber membrane filter. Technically, the drying step is performed in the same manner as one of the blowout steps described above. However, depending on the design of the hollow fiber membrane filter, the drying step is performed for a duration of 900 to 1800 s, or 1100 to 1600 s, or 1200 to 1500 s, or 1250 to 1400 s.

[0037]

[0036] After the drying step, the hollow fiber membrane filter is ready for immediate use. After the drying step, the fluid inlets 102a, 102b, 103a, and 103b are closed with appropriate caps to prevent bacteria from passing through. Preferably, the fluid inlets are sealed under sterile conditions within the connecting devices 150A, 150B, 150C, and 150D.

[0038]

[0037] In a further embodiment, the process according to the present invention is characterized in that the hollow fiber membrane of the hollow fiber membrane filter contains polysulfone and polyvinylpyrrolidone, or consists of polysulfone and polyvinylpyrrolidone.

[0039]

[0038] In a further preferred embodiment, the hollow fiber membrane is prepared by the following method: A spinning solution consisting of 16 parts by weight of polysulfone (P3500 from Solvay), 4.4 parts by weight of polyvinylpyrrolidone (K82-86 from Ashland), and 79.6 parts by weight of DMAC is processed into a homogeneous spinning material under stirring, heating to 60°C, and degassing. The spinning material is extruded through an annular gap nozzle to form a spun yarn surrounding a centrally guided precipitate consisting of 35% DMAC and 65% water. The precipitate is guided inside the hollow spun yarn. The temperature of the annular gap nozzle is 70°C. The extruded spun yarn is passed through a precipitate gap having an atmosphere with a relative humidity of 100%. The height of the precipitate gap is 200 mm, and the residence time in the precipitate gap is set to 0.4 s. The spun yarn is introduced into a precipitation bath consisting of water at 80°C and precipitated to form a hollow fiber membrane. Next, the hollow fiber membrane is passed through a rinsing bath adjusted to a temperature of 75°C to 90°C. After that, the hollow fiber membrane is dried at a temperature of 100°C to 150°C.

[0040]

[0039] Next, in order to construct a hollow fiber membrane filter, the obtained hollow fiber membranes are wound onto a reel and combined to form a fiber arrangement. The wound fiber arrangement is processed into a hollow fiber membrane bundle and used in the manufacture of a hollow fiber membrane filter.

Claims

1. A method for sterilizing a hollow fiber membrane filter having a plurality of hollow fiber membranes, wherein the plurality of hollow fiber membranes are sealed at both ends within a housing of the hollow fiber membrane filter such that a first compartment including the interior of the hollow fiber membranes and a second compartment including the space between the hollow fiber membranes are formed, the hollow fiber membrane filter has at least two fluid inlets connected to the first compartment and at least two fluid inlets connected to the second compartment, the fluid inlets are configured to be connected to a sterilization device, and the method is a) A step of rinsing the hollow fiber membrane filter with a fluid, particularly water, wherein the rinsing fluid passes through the first and second sections of the hollow fiber membrane filter via the selection of the fluid inlet. b) Steps to conduct a leak test, c) Sterilizing the hollow fiber membrane filter with a sterilizing fluid, particularly heated water or steam, wherein the sterilizing fluid passes through the first and second compartments of the hollow fiber membrane filter via the selection of the fluid inlet. It has at least the following features: A method characterized in that the leak test is performed before the sterilization step.

2. The method according to claim 1, characterized in that, in the leak test, sterile compressed air is introduced into the second compartment of the hollow fiber membrane filter, particularly passing through, highly purified water is introduced into the first compartment of the hollow fiber membrane filter, particularly passing through, and the pressure in the second compartment is higher than the pressure in the first compartment.

3. The method according to claim 2, characterized in that the introduction of sterile compressed air into the second compartment of the hollow fiber membrane filter, particularly through which it passes, and the introduction of highly purified water into the first compartment, particularly through which it passes, are carried out in accordance with the principle of countercurrent flow.

4. The method according to any one of claims 1 to 3, characterized in that the temperature of the water passing through the first and second compartments of the hollow fiber membrane filter is 50 to 120°C.

5. The method according to any one of claims 1 to 4, characterized in that the sterilization fluid is water vapor having a temperature of 105 to 150°C, and the water vapor is introduced into the first and second compartments of the hollow fiber membrane filter at a pressure of 1.1 to 3 bar.

6. The method according to any one of claims 1 to 5, characterized in that a blowout step with sterile compressed air is performed between the leak test and the sterilization step, and the first and second compartments of the hollow fiber membrane filter are blown out with sterile compressed air.

7. The method according to any one of claims 1 to 6, characterized in that, prior to the leak test, a steam extrusion step is performed, through which steam enters, in particular, the first and second compartments of the hollow fiber membrane filter.

8. The method according to claim 7, characterized in that the introduction, particularly the passage, of water vapor into the first and second compartments of the hollow fiber membrane filter is carried out by the principle of uniform flow.

9. The method according to claim 7 or 8, characterized in that the steam has a temperature of 100 to 150°C and a pressure of 1.1 to 3 bar.

10. The method according to any one of claims 7 to 9, characterized in that the water vapor in the first compartment and the second compartment of the hollow fiber membrane filter has substantially the same pressure, or the water vapor in the first compartment has a higher pressure than the water vapor in the second compartment.

11. The method according to any one of claims 7 to 10, characterized in that the rinsing step is performed between the steam extrusion step and the leak test before sterilization.

12. The method according to any one of claims 7 to 11, characterized in that a first blowout step, in which the first and second compartments of the hollow fiber membrane filter are blown out with sterile compressed air, is performed before the steam extrusion step.

13. The method according to any one of claims 1 to 12, characterized in that, after the sterilization step, a drying step is performed in which sterile compressed air passes through the first and second compartments of the hollow fiber membrane filter.

14. The process according to any one of claims 1 to 13, characterized in that the hollow fiber membrane contains polysulfone and polyvinylpyrrolidone, or consists of polysulfone and polyvinylpyrrolidone.

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